CCR7 expresion

Inhibition of CCR7 enhances CD8+ T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.

Tumour-residing CCR7 DCs co-localise with PD-1CD8 T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7 DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.

The CAR was designated FHVH33-CD8BBZ...Anti-CAR antibody responses were detected in 4/12 patients assessed. FHVH-T have powerful, rapid, and durable anti-MM activity.

However, the high expression of the CCR7 marker was not related to the tumor size. Conclusion : Based on our results, CCR7 expression in gastric cancer can be considered a clinical prognostic indicator in patients with gastric cancer.

Treating LCH-like cells with RGFP966, an HDAC3-specific inhibitor, increased apoptosis indicated by annexin-V and DAPI staining, reduced expression of Bcl-2, increased CCR7 expression, and decreased S6 phosphorylation (an indication of decreased mTOR activity), showing that pharmacological inhibition of HDAC3 may prove therapeutically efficacious by abrogating pathognomonic features of LCH cells...We further show, HDAC3 is required for multiple pathognomonic features of LCH cells and could be a promising drug target. Furthermore, if HDAC3 is required for the development of pathological DC and DC progenitors, HDAC3 blockade would address a great need in treatment of patients with LCH.

Distinct signatures of T-cell exhaustion and depletion are present in the early post-ASCT period among individuals relapsing within 24 months. Peripheral blood immune phenotyping may identify functionally high-risk patient populations in need of alternative treatment approaches to maintain durable disease control.

The differences in anti-tumour efficacy of CAR-T cells among patients with different clinical outcomes appear to be due to the loss of CCR7 gene expression, coupled with increased expression of activation- and inhibitor-related genes in the CD8 naïve-T cell populations among the apheresis T cells from patients with a poor molecular response. These findings significantly advance our understanding of the underlying molecular determinants of pre-manufacture T cell function.

Taken together, our data suggest that immune exhaustion is one of the major factors impairing T-cell function in sMZL. Our findings highlight the importance of maintaining healthy T-cell pools as a predictor of long-term disease-free intervals and support a rationale for earlier use of T-cell-based therapies.

The Elevated expression level of CCR7 statistically correlated with higher MMP-9 expression (P<0.001). MMP-9 and CCR7 might be beneficial as predictors of lymph node metastasis in LSCC patients.

These data support the hypothesis that K562 AaPCs are an ideal and superior ex vivo expansion platform for generation of activated TILs from sarcoma patients with memory phenotype which have implication for improved efficacy and long-term persistence after adoptive transfer.

In summary, inflammation, and the immune response play an important role in OSCC. All five hub genes were good predictors of OSCC prognosis, suggesting that they could be used as potential therapeutic targets and tumor markers.

The Bruton's tyrosine kinase inhibitor ibrutinib and the B-cell lymphoma 2 anti-apoptotic protein inhibitor venetoclax provide high response rates in chronic lymphocytic leukemia (CLL). Our data indicate that venetoclax treatment did not significantly modify CCR7 expression pattern nor CAP-100 mechanisms of action. Together, these findings support CAP-100 as an adjuvant therapy to venetoclax that may introduce additional modes of action in CLL therapy.

Inhibition of CCL21-CCR7 signaling led to an increased sensitivity to temozolomide-induced tumor cell death. Collectively, our data indicate that drug targeting of CCL21-CCR7 signaling in tumor and TME cells is a therapeutic option against GBM.

CCL19/CCR7 may be a potential novel therapeutic target in gastric cancer.

High CCR7 reduced overall patient survival &lsqb;hazard ratio 2.62 (95% CI 1.59 to 4.32)]. This study showed that high expression of CCR7 in HNSCC tumours was significantly associated with worse clinicopathological and survival outcomes, suggesting that CCR7 and its pathway could be potential therapeutic strategies for HNSCC.

The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC.

We compared specimens from 3 treatment arms for downstream analysis: Arm A: an allogeneic whole cell vaccine, GVAX (n=7); Arm B: GVAX and nivolumab (n=4); Arm C: GVAX, nivolumab, and urelumab (n=4)... Analysis of combination GVAX, PD-1 inhibition and CD137 agonist therapy demonstrated changes in multiple immune cell proportions and their functional pathways. These data provide new evidence that PDACs can become T cell rich and respond to combination immunotherapies.

In addition, we validated genetically and pharmacologically that inhibition of PAK4 kinase activity is sufficient to improve anti-tumor efficacy of anti-PD-1 blockade in multiple melanoma mouse models. Therefore, this study provides novel insights into the mechanism of action of PAK4 inhibition and provides the foundation for a new treatment strategy that aims to overcome resistance to PD-1 blockade by combining anti-PD-1 with a small molecule PAK4 kinase inhibitor.

The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients.

Inhibiting the CCL21/CCR7 interaction by blocking antibodies or using therapeutic ibrutinib altered the adhesion of leukemic cells...Moreover, CCL21, by retaining malignant B cells, provide a protective environment for their niching and survival thus allowing immune tumor survey evasion and resistance to treatment. These findings argue for a specific targeting or re-education of NLCs as a new immunotherapy strategy for this still deadly disease.

The bioinformatic analysis showed a high CCR7 expression associated with the presence of metastasis (FC = 2.6, p = 0.03) in the Cancer Genome Atlas (TCGA) PCa cohort (PRAD). We showed that CCR7 expression in tumors from young patients is associated with the early onset of the disease and could also be related to lymph node metastasis.

The dramatically increased effective function of Tscm but low level in vivo showed that improving the frequencies of Tscm from MM patients may as a potential tumor target long lived T cell therapy tool, which prolongs the survival of MM

CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

Infused leukemic cells colonized less efficiently the lymph nodes of Nfkb2-deficient mice, with no differences in the spleen and liver. Conclusion We conclude that TCR signaling is associated with expression of proteins associated with leukemic dissemination to specific niches and that CCR7 is a potential mediator of that property.

Furthermore, it does not modulate CCR7-driven homing nor nodal interstitial migration. Together, our results support that ibrutinib-induced CLL T-cell accumulation in the blood stream is not derived from an impairment of CCR7-driven recirculation between the SLO and bloodstream, and therefore T-cell expansion is the most plausible cause.

HSP-27 and BAP1 are considered to be associated with metastasis, indicating these proteins as potential treatment targets in metastatic uveal melanoma.

Elevated DARS-AS1 expression enhances cell growth and invasion via regulating CCR7. These data firstly suggested that DARS-AS1 exerted as one oncogene in osteosarcoma partly via regulating miR-532-3p/CCR7.

In the three-dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21-reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand-expressing intra-tumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.

Expression of CCR7 receptor by off-the-shelf t-haNK cells improves their homing toward lymph node chemokines both in vitro and in vivo, resulting in superior tumor control.

MEM-288 drives MEM40 + IFNβ expression in freshly resected human lung tumors and generates potent anti-tumor responses as a monotherapy and in combination with immune checkpoint inhibitors. Furthermore, MEM-288 induced enhancement of tumor-reactive TILs and provides a rationale for studies to determine whether MEM-288 pre-treatment generates a superior TIL product for more effective adoptive T cell therapy.

When co-cultured with the autologous tumor, hypoxic TILs displayed increased IFNγ, TNFα as well as increased Granzyme B release (p<0.001) when compared to TIL expanded in normoxia (20% O2). Collectively, these results support the advantage of adapting TIL to hypoxic conditions in the production of tumor-reactive TIL.

ELC8-83 was used to block this signaling. These studies demonstrate the efficacy of ELC8-83 in blocking signaling in T-ALL and provide a platform for testing ELC8-83 in the mouse model of T-ALL.

The fusion CCL19 protein specifically detected CCR7 expressed in canine lymphoma cell lines, which showed active chemotaxis to both canine and mouse ligands. The present study will help further research on the involvement of canine CCR7 in LN metastasis.

We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.

Here, we review published data to catalogue CCR7 expression across blood cancers and appraise which classical and novel roles are attributed to this receptor in the pathogenesis of specific hematologic neoplasms. We outline why novel therapeutic strategies targeting CCR7 might provide clinical benefits to patients with CCR7-positive hematopoietic tumors.

In models of both subcutaneous and metastatic melanoma, we demonstrate that the dendritic cells sorted for CCR7 expression trigger enhanced CD8 T-cell driven antitumor immune responses which correlate with reduced tumor burden and increased survival. Finally, we demonstrate that this approach is directly translatable to human dendritic cell therapy using the same reagents coupled with clinical-grade flow-cytometric sorting.

In a first-generation trial using ex vivo rapamycin, polyclonal autologous Th1/Tc1 (RAPA-101) cells were safe and associated with delayed relapse when administered after hematopoietic cell transplantation in high-risk MM patients. Now, we are evaluating temsirolimus for manufacture of second-generation RAPA-201 cells...Bridging chemotherapy during manufacturing (Cycle 1) and host conditioning prior to RAPA-201 infusion consisted of the 14-day PC regimen [pentostatin (4 mg/m 2 IV; days 1, 4, 8, 12; dose adjusted/omitted with renal insufficiency); cyclophosphamide (100-200 mg PO, days 1-5 and days 8-12)]...RAPA-201 therapy represents a new paradigm that utilizes stringent mTOR inhibition to reprogram Th1/Tc1 cells for enhanced metabolic fitness and induction of in vivo T cell clonal expansion, thus providing an alternative to gene-modified targeted T cell therapy. With these promising safety and efficacy results, current RAPA-201 developmental efforts are directed towards completing protocol accrual in parallel with the design and implementation of next-generation clinical trials.

We performed flow cytometric studies on ex-vivo stimulated, clinically annotated CART products of patients with large B cell lymphoma from the pivotal ZUMA-1 clinical trial that led to FDA-approved Axicabtagene ciloleucel (Axi-Cel)... Our results indicate that TNFR2 plays a role in early activation and apoptosis initiation of CART19 following CAR stimulation with CD19 + target cells and present TNFR2 knockout as a strategy to enhance CART19 anti-tumor activity.